Abstract This proposal explores a rarely studied pregnancy exposure, invasive placentation (IP), for which we observed suggestive preliminary associations with cancer in other projects. IP is an obstetric condition involving lack of control of the maternal/fetal interface, resulting in cellular invasion of placental tissue into the surrounding tissues. IP may include only the inner layer of the uterus, but may also include all uterine layers and adjacent organs such as the bladder. Specific pathways by which IP occurs are unclear. Women with cesarean deliveries have increased risk of IP, however, not all women with prior cesarean delivery develop IP, and not all women with IP have had prior cesarean delivery. Cellular invasion and breakdown of normal tissue barriers (features of IP) are also features of cancer development. IP may be a marker for women with underlying characteristics that increase cancer susceptibility. Uterine scarring from prior cesarean delivery may provide an anchor for IP development, but only women prone to abnormal cellular invasion/tissue barriers may experience this complication. By extension, their offspring may also possess characteristics that increase cancer risk. The goal of this project is to explore the relationship of IP with cancer in parous women, and as an in utero exposure or marker of cancer susceptibility in children. IP is rare and unlikely to have been systematically recorded in prior cancer studies involving interviews, thus requiring large studies with focused and uniform exposure assessment. Specifically, we propose to use linked health registry data from 3 existing population-based cancer studies to explore the following hypotheses: 1) A history of IP in a previous pregnancy is more common among parous women with breast cancer than among comparison women with deliveries in similar years. Data for this aim include >6,000 breast cancer cases and a large group of matched controls. 2) Childhood cancer cases are more likely than children without cancer to have a mother who experienced IP in their pregnancies. Data for this aim include >5000 childhood cancer cases and a matched control group of children without cancer. 3) IP is more common in women with cancer during pregnancy than among comparison women with deliveries in the same years. Cross-sectional analyses will include >14,000 women with deliveries who have a cancer diagnosis in their hospital discharge record, and a group of women without cancer. For IP cases, we will also conduct medical chart reviews to assess accuracy of the IP diagnosis in the hospital discharge records, and the degree of tissue invasion involved. This project will allow us to efficiently explore the possible IP-cancer association with existing data. Results may lead to further studies with detailed characterization and assay of placental tissue.